Optical and electrochemical DNA nanobiosensors

In the past two decades, nanoscale advanced materials have been explored for biosensing molecules, so new horizons have opened up for identifying and quantifying biomolecules, and possible early diagnosis of diseases.DNA nanobiosensors show promise. This article provides an overview on their optical and electrochemical aspects. We discuss recent progress in this field, describing basic concepts of molecular beacons and quantum dots as optical nano-imaging systems. Also, carbon nanotubes provide a platform for development and advancement of electrochemical DNA nanobiosensors, which are increasingly being implemented as robust tools for detection in biomedical sciences.     

聚合物粒子在生物化学与生物医学中的应用

就亚微米和单粒径两种新型的聚合物粒子在生物化学与生物医学如免疫分析、药物载体、真核细胞、原核细胞及生物大分子产品等的分离等领域中的最新应用进行了综述。     

Molecular luminescence imaging

Imaging techniques relying on different luminescence processes are powerful bioanalytical tools for life sciences. They are used in multiplexed quantitative assays in different analytical formats and to assess the spatial distribution of a given target molecule, chemical or biochemical process in macro- and microsamples, including the in vivo evaluation of biological and pathological processes. Here, recent progresses in luminescence imaging techniques are described, including new labels for fluorescence, time-resolved fluorescence and bio-chemiluminescence, multiplexed imaging microscopy techniques and whole-body luminescence imaging in live animals.     

Data-processing strategies for metabolomics studies

Metabolomics studies aim at a better understanding of biochemical processes by studying relations between metabolites and between metabolites and other types of information (e.g., sensory and phenotypic features). The objectives of these studies are diverse, but the types of data generated and the methods for extracting information from the data and analysing the data are similar. Besides instrumental analysis tools, various data-analysis tools are needed to extract this relevant information. The entire data-processing workflow is complex and has many steps. For a comprehensive overview, we cover the entire workflow of metabolomics studies, starting from experimental design and sample-size determination to tools that can aid in biological interpretation. We include illustrative examples and discuss the problems that have to be dealt with in data analysis in metabolomics. We also discuss where the challenges are for developing new methods and tailor-made quantitative strategies.     

Optische Einzelmolekülspektroskopie. Einblicke in den Nanokosmos

Single‐molecule fluorescence spectroscopy evolved to a variety of tools to investigate molecular dynamics in thermodynamic equilibrium and to reveal subpopulations in heterogeneous molecular distributions which usually remain hidden in bulk experiments. Applications of single‐molecule experiments range from life sciences and material sciences to photo‐physics and photo‐chemistry. Some of these research fields, like chemical catalysis, have just recently been entered. This article summarizes major principles of single‐molecule fluorescence spectroscopy and gives an overview on some important applications up to the development of novel microscopic techniques with nanometer resolution.     

Recent applications of liquid chromatography-mass spectrometry in forensic science

Recent years have seen the development of powerful technologies that have provided forensic scientists with new analytical capabilities, unimaginable only a few years ago. With liquid chromatography-mass spectrometry (LC-MS) in particular, there has been an explosion in the range of new products available for solving many analytical problems, especially for those applications in which non-volatile, labile and/or high molecular weight compounds are being analysed. The aim of this article is to present an overview of some of the most recent applications of LC-MS (/MS) to forensic analysis. To this end, our survey encompasses the period from 2002 to 2005 and focuses on trace analysis (including chemical warfare agents, explosives and dyes), the use of alternative specimens for monitoring drugs of abuse, systematic toxicological analysis and high-throughput analysis. It is not the intention to provide an exhaustive review of the literature but rather to provide the reader with a 'flavour' of the versatility and utility of the technique within the forensic sciences.     

Clinical Chemistry: Challenges for Analytical Chemistry and the Nanosciences from Medicine

Clinical chemistry and laboratory medicine can look back over more than 150 years of eventful history. The subject encompasses all the medicinal disciplines as well as the remaining natural sciences. Clinical chemistry demonstrates how new insights from basic research in biochemical, biological, analytical chemical, engineering, and information technology can be transferred into the daily routine of medicine to improve diagnosis, therapeutic monitoring, and prevention. This Review begins with a presentation of the development of clinical chemistry. Individual steps between the drawing of blood and interpretation of laboratory data are then illustrated; here not only are pitfalls described, but so are quality control systems. The introduction of new methods and trends into medicinal analysis is explored, along with opportunities and problems associated with personalized medicine.     

A Rotational BODIPY Nucleotide: An Environment‐Sensitive Fluorescence‐Lifetime Probe for DNA Interactions and Applications in Live‐Cell Microscopy

Fluorescent probes for detecting the physical properties of cellular structures have become valuable tools in life sciences. The fluorescence lifetime of molecular rotors can be used to report on variations in local molecular packing or viscosity. We used a nucleoside linked to a meso‐substituted BODIPY fluorescent molecular rotor ( dC^bdp ) to sense changes in DNA microenvironment both in vitro and in living cells. DNA incorporating dC^bdp can respond to interactions with DNA‐binding proteins and lipids by changes in the fluorescence lifetimes in the range 0.5–2.2 ns. We can directly visualize changes in the local environment of exogenous DNA during transfection of living cells. Relatively long fluorescence lifetimes and extensive contrast for detecting changes in the microenvironment together with good photostability and versatility for DNA synthesis make this probe suitable for analysis of DNA‐associated processes, cellular structures, and also DNA‐based nanomaterials.     

Proof of the Fukui conjecture via resolution of singularities and related methods: III

The present article is a direct continuation of the second part of this series. In conjunction with the analysis of the energy band curves of carbon nanotubes, we develop here fundamental theoretical tools, which are essential to prove the Local Analyticity Proposition (LAP). The LAP enables one to prove the Fukui conjecture (the guiding conjecture for developing the repeat space theory) in a new and powerful context of the theory of algebraic curves and resolution of singularities. The present fundamental tools also serve as modular tools for the repeat space theory, by which one can solve a variety of additivity and molecular network problems in a unifying manner.     

Bioanalysis in structured microfluidic systems

Microfluidic and lab-on-a-chip devices have attracted widespread interest in separation sciences and bioanalysis. Recent designs in microfluidic devices extend common separation concepts by exploiting new phenomena for molecular dynamics on a length scale of 10 mum and below, giving rise to novel manipulation tools and nonintuitive phenomena for microseparations. Here, we focus on three very recent developments for bioseparations based on tailored microfluidic systems: Single cell navigation, trapping and steering with subsequent on-chip lysis, protein separation and LIF detection (Section 3.1), then we report dielectrophoretic trapping and separation of large DNA fragments in structured microfluidic devices (Section 3.2). Finally, a paradoxial migration phenomenon based on thermal fluctuations, periodically arranged microchannels and a biased alternating current electric field is presented in Section 3.3.     

Swarm intelligence metaheuristics for enhanced data analysis and optimization

The swarm intelligence (SI) computing paradigm has proven itself as a comprehensive means of solving complicated analytical chemistry problems by emulating biologically-inspired processes. As global optimum search metaheuristics, associated algorithms have been widely used in training neural networks, function optimization, prediction and classification, and in a variety of process-based analytical applications. The goal of this review is to provide readers with critical insight into the utility of swarm intelligence tools as methods for solving complex chemical problems. Consideration will be given to algorithm development, ease of implementation and model performance, detailing subsequent influences on a number of application areas in the analytical, bioanalytical and detection sciences.     

半导体荧光量子点标记技术

生命体系中化学、生物信息的活体、原位、实时、动态和高灵敏获取,是当前生命科学研究中迫切需要解决的关键问题之一,发展相关的新技术与新方法至关重要。半导体荧光量子点因其优异的荧光特性可望在解决此类难题中发挥重要作用而日益受到关注。本文将根据我们课题组多年来的研究工作经验,就半导体荧光量子点标记技术的相关基础问题、在生物医学领域中的应用以及发展前景等做简要评述。     

Deuterium‐ and Tritium‐Labelled Compounds: Applications in the Life Sciences

Hydrogen isotopes are unique tools for identifying and understanding biological and chemical processes. Hydrogen isotope labelling allows for the traceless and direct incorporation of an additional mass or radioactive tag into an organic molecule with almost no changes in its chemical structure, physical properties, or biological activity. Using deuterium‐labelled isotopologues to study the unique mass‐spectrometric patterns generated from mixtures of biologically relevant molecules drastically simplifies analysis. Such methods are now providing unprecedented levels of insight in a wide and continuously growing range of applications in the life sciences and beyond. Tritium (³H), in particular, has seen an increase in utilization, especially in pharmaceutical drug discovery. The efforts and costs associated with the synthesis of labelled compounds are more than compensated for by the enhanced molecular sensitivity during analysis and the high reliability of the data obtained. In this Review, advances in the application of hydrogen isotopes in the life sciences are described.     

Protein glycosylation: new challenges and opportunities

Protein glycosylation is the most complex post-translational modification process. More than 50% of proteins in humans are glycosylated, while bacteria such as E. coli does not have this modification machinery. Many small-molecule natural products also require glycosylation in order to express their function. Development of effective synthetic tools for use in understanding the effect of glycosylation on the structure and function of biomolecules will lead to the development of new strategies to tackle major problems associated with carbohydrate-mediated biological recognitions.     

Multistage isothermic sequencing by hybridization

Despite the impressive progress in many areas of biological sciences reading DNA sequences still remains one of the most important problems. One of the methods of DNA sequencing is sequencing by hybridization which is composed of two stages--the biochemical one and the computational one. Although this method is quite modern it suffers sensitivity to errors appearing in the biochemical stage. This is a motivation for developing some new variants of the method which should be more resistant to errors of these types. Two of such non-standard approaches are multistage and isothermic sequencing by hybridization. Each of the methods is less sensitive to some types of the errors appearing in the biochemical stage, in comparison to the standard version of the method, but on the other hand, they are more sensitive to remaining types of errors. However, a combination of the two approaches reduces the sensitivity of the components.     

Symmorphy transformations and operators in the repeat spaceX r(q) for additivity problems

A theoretical framework has been presented, which links two diverse molecular problems: the study of symmorphy transformations of molecular shape analysis (further developed in the present paper) and that of additivity of the zero-point vibrational energy of hydrocarbons and the total pi-electron energy of alternant hydrocarbons. The linkage, using fundamental tools of (general) topology and algebra, makes it possible to mutually introduce the methodologies used in fields hitherto separately investigated. By establishing this linkage, topological patterns described by symmorphy groups can be treated by the algebraic methods developed for the above additivity problems. The linkage also brings forth new techniques of topologizing the repeat spaceX _r(q) for the additivity problems. Moreover, this connection paves the way to analyzing molecular homologous series and their properties by means of associating sequences of molecular structures with elements of a repeat space equipped with a topology.On leave from: Institute for Fundamental Chemistry, 34-4 Nishihiraki-cho, Takano, Sakyo-ku, Kyoto 606, Japan.     

Perfluoroaryl and Perfluoroheteroaryl Reagents as Emerging New Tools for Peptide Synthesis,Modification and Bioconjugation

Peptides and proteins are becoming increasingly valuable as medicines, diagnostic agents and as tools for biomedical sciences. Much of this has been underpinned by the emergence of new methods for the manipulation and augmentation of native biomolecules. Perfluoroaromatic reagents are perhaps one of the most diverse and exciting tools with which to modify peptides and proteins, due principally to their nucleophilic substitution chemistry, high electron deficiency and the ability for their reactivity to be tuned towards specific nucleophiles. As discussed in this minireview, in recent years, perfluoroaromatic reagents have found applications as protecting groups or activating groups in peptide synthesis and as orthogonal handles for peptide modification. Furthermore, they have applications in chemoselective ‘tagging’, stapling and bioconjugation of peptides and proteins, as well as tuning of ‘drug-like’ properties. This review will also explore possible future applications of these reagents in biological chemistry.     

Nucleic Acid‐Barcoding Technologies: Converting DNA Sequencing into a Broad‐Spectrum Molecular Counter

The emergence of high‐throughput DNA sequencing technologies sparked a revolution in the field of genomics that has rippled into many branches of the life and physical sciences. The remarkable sensitivity, specificity, throughput, and multiplexing capacity that are inherent to parallel DNA sequencing have since motivated its use as a broad‐spectrum molecular counter. A key aspect of extrapolating DNA sequencing to non‐traditional applications is the need to append nucleic‐acid barcodes to entities of interest. In this review, we describe the chemical and biochemical approaches that have enabled nucleic‐acid barcoding of proteinaceous and non‐proteinaceous materials and provide examples of downstream technologies that have been made possible by DNA‐encoded molecules. As commercially available high‐throughput sequencers were first released less than 15 years ago, we believe related applications will continue to mature and close by proposing new frontiers to support this assertion.     

Target-specific chemical acylation of lectins by ligand-tethered DMAP catalysts

Because sugar-binding proteins, so-called lectins, play important roles in many biological phenomena, the lectin-selective labeling should be useful for investigating biological processes involving lectins as well as providing molecular tools for analysis of saccharides and these derivatives. We describe herein a new strategy for lectin-selective labeling based on an acyl transfer reaction directed by ligand-tethered DMAP (4-dimethylaminopyridine). DMAP is an effective acyl transfer catalyst, which can activate an acyl ester for its transfer to a nucleophilic residue. To direct the acyl transfer reaction to a lectin of interest, we attached the DMAP to a saccharide ligand specific for the target lectin. It was clearly demonstrated by biochemical analyses that the target-selective labeling of Congerin II, an animal lectin having selective affinity for Lactose/LacNAc (N-acetyllactosamine), was achieved in the presence of Lac-tethered DMAPs and acyl donors containing probes such as fluorescent molecules or biotin. Conventional peptide mapping experiments using HPLC and tandem mass-mass analysis revealed that the acyl transfer reaction site-specifically occurred at Tyr 51 of Cong II. This strategy was successfully extended to other lectins by changing the ligand part of the ligand-tethered DMAP. We also demonstrated that this labeling method is applicable not only to purified lectin in test tubes, but also to crude mixtures such as E. coli lysates or homogenized animal tissue samples expressing Congerin.     

Cyclodextrins in capillary electrophoresis enantioseparations--recent developments and applications

Capillary EKC has been established as a versatile and robust CE method for the separation of enantiomers. Within the chiral selectors added to the BGE CDs continue as the most widely used selectors due to their structural variety and commercial availability. This is reflected in the large number of practical applications of CDs to analytical enantioseparations that have been reported between January 2006 and January 2008, the period of time covered by this review. Most of these applications cover aspects of life sciences such as drug analysis, bioanalysis, environmental analysis, or food analysis. Moreover, new CD derivatives have been developed in an attempt to achieve altered enantioselectivities and to further broaden the application range. Finally, efforts will be summarized that aim at an understanding of the molecular level of the chiral recognition between CDs and the analytes.